Airborne Preventive Measures to Reduce New TB Infections in Household Contacts

Tuberculosis (TB) is currently one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent (ranking above HIV/AIDS). In 2018, an estimated 10 million people fell ill with TB worldwide, and more than 1.4 million people died from it, making eradication of this disease in the next decades highly unlikely unless new interventions are discovered. Mycobacterium tuberculosis (Mtb) transmission mainly occurs when patients affected by laryngeal or pulmonary TB cough upon others and the mycobacteria are spread in airborne droplets nuclei smaller than 5 μm that are subsequently inhaled by close contacts. Although chemoprophylaxis once a new TB infection is detected is an effective strategy to reduce the risk of contacts developing active TB, it does not prevent Mtb acquisition; it only reduces the risk of developing active TB once infected. Currently, the large majority of international guidelines recommend strict measures to reduce airborne transmission in hospitalized patients with pulmonary TB, with a minimum of 2 weeks of effective TB therapy to consider a patient no longer infectious and discontinue respiratory isolation in healthcare settings. On the contrary, in the community, no special recommendations regarding protection of household contacts are specified, assuming that most of them are already infected and that the TB index case will stop infecting very quickly under antimicrobial treatment. However, several studies show that median time to sputum Mtb culture conversion under effective treatment takes 5-7 weeks, raising the potential for continued transmission even despite effective treatment. Furthermore, a previous study has shown that in Santiago, Chile, 55% of household contacts of TB cases have no evidence of TB infection at the time of diagnosis of the index case - as categorized by negative latent TB testing - yet under close follow-up, up to 21% of these show new evidence of having acquired the infection based on latent TB test conversion after 12 weeks of follow-up. The investigators hypothesize that reducing respiratory exposure within the household, during the first weeks of TB treatment initiation of the index case, can reduce new TB infections in close contacts. For this purpose, a pilot, controlled, pre-post study will be done to evaluate the feasibility of implementing a bundle of respiratory precautions to all household contacts of new pulmonary TB cases, compared to standard of care, in primary care in a high TB incidence area in Santiago. The respiratory bundle in the intervention arm will be implemented as soon as a new pulmonary TB case is diagnosed, will last 2 weeks and, will include: (a) provision of N95 masks and strong recommendation of use to all household contacts and the index case when sharing a room together, (b) recommendation to index case to sleep in a room alone, with the door closed and avoid sharing room with others, (c) promotion of strategies to improve house ventilation; and (d) education about TB transmission. The investigators expect to show that this trial is feasible to proceed with a larger, definitive cluster randomized controlled trial that will evaluate the intervention effectiveness in reducing the incidence of new TB infections in household contacts. The results of this study will help to answer a critical research gap in TB infection control and prevention and, it will provide a key contribution to future policies regarding TB control and elimination worldwide. Furthermore, in the new global context of rising infectious agents of pandemic risk, this work may have an additional potential relevance with respect to the use, acceptability and transmission prevention potential of a respiratory bundle in the household setting regarding other respiratory pathogens such as SARS-Cov-2.